The long-term goal of this project is to develop a new technology to improve the screening for and diagnosis of breast cancer. Non-invasive electrical impedance measurements that are made using a hand-held probe have been shown to improve the specificity and sensitivity of mammography for breast tumor diagnosis in patients with ambiguous mammograms. This non-invasive technology poses no known risks to the subject, and provides a new diagnostic parameter to assess suspicious anomalies. This new technology, called Electrical Impedance Tomography (EIT), makes images of the interior of the body by applying electrical signals to electrodes applied to the skin. These signals cause small electric currents to flow in the body and the voltage and current values at the electrodes are used by mathematical algorithms to reconstruct the values of the electrical conductivity and permittivity inside the body. These reconstructed conductivity and permittivity values can be presented as EIT images. When this is done using several different signal frequencies, the technique is called Electrical Impedance Spectroscopy (EIS), and further diagnostic information may be elucidated. We propose to determine the feasibility of improving the diagnostic ability of mammography by combining a 3-D tomosynthesis mammography system with an EIT/EIS system in order to make simultaneous, in-registration images of breast electrical properties using data collected from two parallel arrays of radiolucent electrodes applied to the mammogram compression plates. We have implemented an electronic instrument, built radiolucent electrode arrays, and written algorithms to reconstruct EIT images for a region of interest within the breast that lies between electrode arrays attached to the compression plates of an x-ray mammography unit. The system operates at frequencies between 3 kHz and 1 MHz, has 60 electrodes, and forms and displays images at 2.5 frames/second. It is being applied to patients undergoing biopsy for breast cancer diagnosis. We have identified a parameter that is calculated from the EIS data that has a markedly different value at the cancer sites in four of four breasts with carcinoma within the ROI, when compared to its value in 44 non-malignant breasts. These findings are confirmed by biopsy and 3-D tomosynthesis mammography. There is nearly no overlap between the values of this parameter with cancer and values in normal tissue or the benign lesions studied so far. We have also developed a display method that superimposes a semi-transparent color over a mammogram image to show the magnitude of this malignancy measure. This is a proposal to continue these studies in more patients with improved hardware, reconstruction algorithms and analysis and display methods. If this combined EIT/EIS/Tomosynthesis system can improve the sensitivity and specificity of mammography for breast cancer screening, it will have a major impact on the ability to detect and treat this major cause of mortality. PUBLIC HEALTH RELEVANCE This project seeks to develop a means to improve the diagnosis of breast cancer by improving the sensitivity and specificity of mammography. Mammography screening reduces breast cancer mortality, but it remains a technology that could be improved. This project seeks to refine Electrical Impedance Tomography as a diagnostic modality, and to develop a scientific basis to justify a large-scale clinical trial of the technique. Success of such a trial would reduce the need for biopsy and increase the detection of tumors at an earlier stage, which would reduce the morbidity and mortality of breast cancer.